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BIG PHYSICS, BIG QUESTIONS –

Blood from human babies makes brains of elderly mice young again

Fountain of youth?

Edelmann/Science Photo Library

By Alice Klein

Do you feel like your brain is getting sluggish with age? A protein found in umbilical cord blood may help restore its youthful vigor.

Researchers have previously found that blood from human teenagers can rejuvenate memory and cognition in elderly mice, probably due to factors present in the plasma – the liquid portion of the blood. Now, blood harvested from babies’ umbilical cords has been found to have even stronger anti-ageing effects.

Joseph Castellano at Stanford University in California and his colleagues discovered this by collecting blood from people at three different life stages – babies, young people around the age of 22, and older people around the age of 66 – and injecting the plasma component into mice that were the equivalent of around 50 years old in human years.

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The most dramatic effects occurred when these mice received babies’ cord plasma. They became faster learners and were better at remembering their way through a maze. This corresponded with enhanced activity in their hippocampi – the brain regions responsible for learning and memory.

Mice that received young people’s plasma also had modest improvements in hippocampus function, but those that received plasma from older adults showed no such improvement. This suggests that human plasma gradually loses its rejuvenating potential with age.

Magic ingredient?

Castellano’s team found that umbilical cord plasma contains more of a protein called TIMP2, and levels in the blood decline with age – a hint that this protein may be responsible for young blood’s rejuvenating properties.

Sure enough, injecting old mice with TIMP2 alone boosted their hippocampus activity and improved their maze-navigation. It also restored their ability to make a nest – a skill that older mice lose.

Moreover, old mice that were treated with cord plasma that had been stripped of TIMP2 showed no cognitive improvement, confirming that the protein is responsible for the strong anti-ageing effect.

The mechanism by which TIMP2 improves cognition is still unclear, but it is known to inhibit a group of enzymes called matrix metalloproteinases, some of which are involved in the progression of Alzheimer’s disease.

The protein may have potential as a treatment for age-related cognitive decline and Alzheimer’s disease. Using TIMP2 as a treatment would be better than using cord plasma itself because it can be synthesised in a lab, avoiding the need for donor supplies, says Castellano.

Plasma in the clinic

But first, we need to understand what TIMP2 does to the hippocampus, says Colin Masters at the University of Melbourne in Australia. “There’s a long way to go before showing that it has any therapeutic potential,” he says.

Several teams are already experimenting with blood plasma. A trial is under way at a hospital in South Korea to test whether injections of human umbilical cord plasma have anti-ageing effects in healthy people aged 55 or older. The final results are due to be collected in August.

Still, injections of donated cord blood plasma may not be the wonder-drug they sound like. There is a risk that growth factors in cord plasma might induce cancer in older people, says Castellano.

He now plans to investigate how declining TIMP2 affects cognitive capacity and Alzheimer’s disease. “If and when TIMP2 looks promising as a possible therapy, I’d imagine there would be a great deal of interest,” says Castellano. “As the ageing population grows each year, I think we’ll increasingly need to look for ways to limit the harmful effects of ageing.”